Recent work has suggested that disruption of the intestinal epithelium in the acute phase of HIV infection is associated with systemic immune activation and loss of intestinal followed by systemic CD4+ T cells. The mechanism by which HIV disrupts intestinal epithelial cells (lECs) has not been determined, nor is it known if effects of HIV on the intestinal epithelium are indirect, direct, or both. Epithelial HIV penetration has been reported for human oral epithelial cells (HOECs) using in vitro studies to demonstrate that oral epithelial cells are susceptible to cell free and cell-associated HIV challenge. In contrast, epidemiological evidence indicates that exogenous infection with HIV-1 through oral tissue epithelium is an uncommon event;certainly when compared to the risks for infection through either the genital or rectal mucosa. Given the differential susceptibilities of various tissue mucosa to HIV infection, understanding the role the epithelium plays in protection against HIV infection is important. We hypothesize that oral mucosal epithelium compared to intestinal epithelium has inherent properties that contribute to its resistance to HIV-1 transcytosis and subsequent infection. The proteome of oral and intestinal epithelial cells in HIV-seropositive subjects compared to uninfected subjects has not been defined. In addition to potential epithelial innate response elements that could elicit protection against HIV-1, we must also consider impaired cellular responses in HIV+ subjects that can be confounded by co-infections such as hepatitis C virus (HCV), commonly found in drug abusive HIV4" individuals. Using 2D-DIGE assessment of HOECs from HIV+ and HIV individuals, we identified differential protein expression profiles between HIV-infected and non-infected individuals. Understanding the role that the epithelium plays in HIV infection and inherent differential susceptibility properties of epithelial tissues derived from various anatomic locations is therefore of interest. The specific aims of this pilot and feasibility study are to: 1.)Compare proteomic profiles of human oral epithelial cells (HOECs) and intestinal epithelial cells (lECs) from HIV, HIV+(on HAART), HIV*/HCV+(on HAART) and HCV* subjects, and 2.) Compare proteomic profiles of (HIV) HOECs and lECs challenged in vitro with HIV, and opioids.